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Trends in cancer survival in 11 European populations from 1990 to 2009: a model-based analysis
original article
Annals of Oncology 20: 564–573, 2009 doi:10.1093/annonc/mdn639 Published online 9 December 2008
Trends in cancer survival in 11 European populations from 1990 to 2009: a model-based analysis A. Gondos1*, F. Bray2, T. Hakulinen3, H. Brenner1 & the EUNICE Survival Working Group 1
Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Heidelberg, Germany; 2Cancer Registry of Norway, Institute of Populationbased Cancer Research, Montebello, Oslo, Norway; 3Finnish Cancer Registry, Helsinki, Finland
Received 11 July 2008; accepted 25 August 2008
Background: The timely provision and interpretation of trends in population-based cancer survival estimates is an important clinical and public health priority.
original article
Materials and methods: We examined survival trends between 1990–1994 and 2000–2004 for 15 common cancers in 10 countries from diverse areas of Europe and provide projected survival estimates for 2005–2009, using novel techniques of model-based period analysis. Results: Between 1990–1994 and 2000–2004, the 5-year relative survival increased significantly in all participating registries among patients with prostate, breast, and colorectal cancers and in at least 7 of 11 registries for stomach, corpus uteri, ovarian, kidney, and thyroid cancers, as well as for non-Hodgkin’s lymphoma. Projections suggest further substantial increases in survival in the calendar period 2005–2009. For most cancer sites amenable to effective early detection and treatment, major geographical differences persist with lower survival in Eastern European countries. Conclusions: Model-based period analysis may be useful in providing population-based cancer survival estimates for currently diagnosed cancer patients. Concerted efforts in the organisation and quality control of cancer care will be very important to achieving further improvements in cancer control in Europe, and improving outcomes in Eastern European populations remains a priority. Key words: cancer registries, neoplasms, survival
introduction
materials and methods
Commonly, a delay of 2–3 years in the availability of population-based cancer incidence data is generally unavoidable due to the time required to attain high completeness in the registration of recent cancer information. In a previous evaluation, it was shown that model-based period analysis, on incorporating long-term survival trends into the modelling of period relative survival estimates, enabled a reliable projection of survival estimates into the near future, compensating for the delay in the general provision of such estimates [1]. We applied model-based period analysis to examine trends in survival and obtain up-to-date cancer survival estimates applying the latest survival analysis techniques in combination with most up-to-date cancer registry data to provide the most timely monitoring of population-based cancer survival. The work was carried out within the framework of the EUNICE Survival Working Group, a mutual effort of 12 population-based cancer registries across Europe.
data sources
*Correspondence to: Dr A. Gondos, Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Bergheimer Str. 20, 69115 Heidelberg, Germany. Tel: +49-6221-548125; Fax: +49-6221-548142; E-mail: [email protected]
The database included relevant cancer information from 11 cancer registries with incidence and follow-up data from at least 1985 onwards. The inclusion criteria and data preparation were described in detail elsewhere [2]. Here, malignant tumours diagnosed in 1985–2004 formed the survival database, along with corresponding age, sex, and calendar period-specific life tables to enable the calculation of relative survival estimates. Table 1 provides an overview of the included registries, their underlying populations, the timeframe of the registry-specific incidence, follow-up data, and background mortality data, as utilised in this analysis.
survival analysis Five-year relative survival estimates were calculated for selected important cancers. Relative survival estimates, which quantify cancer-related excess mortality within a cancer patient population, were derived as ratios of the observed survival of the cancer patients and the expected survival of the underlying general population [3]. The latter estimate was calculated according to the Ederer II method [4]. All derived survival estimates were period estimates, which are exclusively on the basis of the survival experience of patients during the specific calendar period for which they are derived [5], and were shown to closely predict survival later observed for patients diagnosed in that period [6–8].
ª The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected]
original article
Annals of Oncology
Table 1. Participating cancer registries, underlying populations, national coverage percentage, applicable incidence and follow-up years, and life tables utilised in this analysis Registry
Country
Registry underlying population (millions)
National coverage (%)
Incidence First Last year year
Follow-up Date of last follow-up
Life tables Life tables utilised in this analysis
Cracowa Estonia Slovenia Torino Tuscany Eindhoven Scotlandb Finland Norway Geneva Saarlandc
Poland Estonia Slovenia Italy Italy The Netherlands UK Finland Norway Switzerland Germany
0.8 1.4 1.9 1.0 1.2 1.0 5.1 5.2 4.5 0.4 1.0
1.9 100 100 1.8 2.1 6.6 100 100 100 5.3 1.3
1985 1985 1985 1985 1985 1985 1985 1985 1985 1985 1985
31/12/2004 31/12/2004 31/12/2004 31/12/2004 31/12/2004 31/12/2004 31/12/2004 31/12/2004 31/12/2004 31/12/2004 31/12/2004
1990–1991, 1990–1994, 1990–1994, 1990–1994, 1990–1994, 1990–1994, 1986–1991, 1986–1990, 1990–1994, 1990–1994, 1990–1994,
2004 2003 2003 2004 2003 2004 2004 2004 2004 2004 2004
1995–1999, 1995–1999, 1995–1999, 1995–1999, 1995–1999, 1995–1999, 1992–1997, 1991–1995, 1995–1999, 1995–1999, 1995–1999,
2000–2004 2000–2004 2000–2004 2000–2004 2000–2003 2000–2004 1998–2003 1996–2000, 2001–2004 2000–2004 2000–2004 2000–2004
a
Life table data for Poland from the HLD (www.lifetable.de) were used; for calendar years with no corresponding life table data, the life tables of the preceding or following periods were used. b All data for Scotland were on the basis of the data available from the HLD. c Life tables were derived from mortality data by the authors. HLD, Human Life-Table Database.
survival trends between 1990–1994 and 2005–2009 First, 5-year relative survival estimates were calculated for the calendar periods 1990–1994, 1995–1999, and 2000–2004: after age group-specific person-time at risk and number of deaths by year of follow-up were calculated for each period separately (i.e. 1990–1994, 1995–1999, and 2000–2004), a period-specific Poisson regression model for relative survival was used to model the excess number of deaths as a function age group (categorical variable) and follow-up year (categorical variable), using the logarithm of the person-time at risk as the offset. To derive a test of survival trends as well as projected survival estimates, the age group-specific persontime at risk and numbers of deaths by year of follow-up for the periods 1990–1994, 1995–1999, and 2000–2004 were combined and used in a common Poisson regression model, in which calendar period was included as an additional numerical term (1990–1994 = 1, 1995–1999 = 2, 2000–2004 = 3). Projected age group-specific excess number of deaths for each year of follow-up in the period 2005–2009 were obtained assuming that the trend from the periods 1990–1994 to 2000–2004 would continue into the next period. Five-year cumulative relative survival estimates were calculated by multiplication of conditional survival estimates predicted from the regression models for each year of follow-up. In both the period-specific and trend analyses, in instances where registries had data available on incident cases until 2003, but follow-up of vital status until 2004, hybrid analysis was used. The method enables estimation of up-to-date survival for situations where mortality data are available for more recent periods than incidence [9, 10]. Standard errors of the survival estimates were calculated using the delta method. Alpha = 0.05 was used as level of significance for trend tests.
age adjustment All survival estimates were age-adjusted, on the basis of five age groups (15–44, 45–54, 55–64, 65–74, 75+ years), with the exception of prostate cancer, for which the first age group was 15–54 years, and thyroid cancer, for which only two age groups were used (15–44, 45+). Adjustment was done by deriving weighted averages of modelled age-specific 5-year relative survival estimates, with weights from the International Cancer Survival
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Standards [11]. All calculations were carried out using the SAS statistical software package [12].
sponsors The funding source had no involvement in the carrying out this study.
results long-term trends in 5-year relative survival Tables 2–6 present in a uniform layout, age-adjusted 5-year relative survival estimates for 1990–1994, 1995–1999, 2000– 2004, along with model-based projected survival estimates for the calendar period 2005–2009 for the major gastrointestinal, gynaecological, urological, haematological, and other common cancers, respectively. Standard errors for the survival estimates and P values for the survival trend between 1990–1994 and 2000–2004 are also provided. trends in major gastrointestinal cancers Between 1990–1994 and 2000–2004, the 5-year relative survival of patients diagnosed with stomach and colorectal cancers rose significantly in nine and 11 of 11 registries, respectively (Table 2). Among patients with stomach cancer, major increases (of between 5% and 9% units) occurred in Saarland, Slovenia, Torino, Estonia, and Tuscany. In 2000–2004, survival was highest in Saarland (37%), while estimates ranged between 33% and 24% elsewhere, but were lower in Eindhoven (21%), Cracow, and Scotland (both 18%). Projections for the calendar years 2005–2009 predict 5-year relative survival between 19% and 40% in the participating registry populations. Increases in the survival of patients with colorectal cancer were highest, exceeding 10% units, in Cracow, Torino, Estonia, Saarland, Slovenia, and Scotland. Elsewhere, increases were
doi:10.1093/annonc/mdn639 | 565
original article
Annals of Oncology
Table 2. Trends in age-adjusted 5-year relative survival of patients diagnosed with stomach and colorectal cancers, 1990–1994 to 2000–2004, and modelbased projected survival for 2005–2009, by registry
Stomach Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland Colorectal Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland
1990–1994 PE
SE
1995–1999 PE
15.9 19.2 18.1 25.4 28.1 23.6 14.1 24.6 23.6 26.7 27.7
1.7 0.9 0.9 1.5 1.0 1.8 0.6 0.7 0.8 3.1 1.5
22.5 36.1 35.9 45.7 51.1 53.2 42.9 50.2 51.9 54.6 50.7
1.6 1.1 0.9 1.1 0.9 1.3 0.5 0.6 0.5 1.9 1.0
Changea
SE
2000–2004 PE
SE
19.1 20.8 19.6 28.5 30.8 21.5 15.1 26.4 21.7 38.1 29.5
1.7 1.0 0.9 1.6 1.1 1.3 0.6 0.8 0.9 3.7 1.6
17.9 24.1 24.3 30.6 32.8 21.0 17.7 27.7 25.3 25.9 36.8
2.0 1.1 1.0 1.7 1.2 1.2 0.7 0.8 1.0 3.3 1.8
34.9 42.6 38.9 55.2 56.3 53.7 48.2 55.5 55.6 58.7 54.3
1.7 1.1 0.8 1.1 0.8 0.9 0.5 0.6 0.5 1.7 1.0
38.7 49.1 46.9 58.3 59.7 56.2 53.5 57.9 59.2 63.5 61.9
1.6 1.1 0.8 1.0 0.8 0.8 0.5 0.6 0.5 1.7 0.9
P value for trend
2005–2009 PE
SE
2.0 4.9 6.2 5.2 4.7 22.6 3.6 3.1 1.7 20.8 9.1
0.01 <0.01 <0.01 <0.01 <0.01 0.08 <0.01 <0.01 0.02 0.35 <0.01
23.2 26.5 26.1 34.3 34.1 19.1 20.9 29.7 26.0 33.7 39.7
2.5 1.4 1.3 2.1 1.4 1.7 0.9 1.1 1.2 4.9 2.3
16.2 13.0 11.0 12.6 8.6 3.0 10.6 7.7 7.3 8.9 11.2
<0.01 <0.01 <0.01 <0.01 <0.01 0.03 <0.01 <0.01 <0.01 <0.01 <0.01
52.4 57.1 51.7 64.8 64.1 57.2 58.6 62.3 61.9 67.1 66.6
2.1 1.4 1.1 1.2 1.0 1.2 0.6 0.8 0.6 2.2 1.2
a
Change in the 5-year relative survival between 1990–1994 and 2000–2004, in % units PE, point estimate; SE, standard error.
close to 10% units in Geneva, Tuscany, Finland, and Norway, while estimates rose by 3% units in Eindhoven. In the 2000–2004 period, survival exceeded or essentially reached 60% in Geneva, Saarland, Norway, Tuscany, Torino, and Finland, ranged between 56% and 53% in Eindhoven and Scotland, but remained <50% in Estonia (49%), Slovenia (47%), and Cracow (39%). Projections for 2005–2009 predict ongoing survival increases in all registries except Eindhoven, with estimates reaching 65% in Geneva, Saarland, and Torino, and exceeding 60% in Finland and Norway.
breast and female genital cancers Between 1990–1994 and 2000–2004, the 5-year relative survival of patients diagnosed with breast, corpus, and ovarian cancers rose significantly in 11, 8, and 9 registries, respectively (Table 3). Among patients with breast cancer, increases in survival were largest in Cracow with +19% units, while increases were between 10% and 12% units in Scotland, Slovenia, Geneva, and Eindhoven, and between 8% and 6% units in the remaining registries. By 2000–2004, survival estimates ranged between 87% and 80% in Geneva, Tuscany, Torino, Finland, Norway, Eindhoven, and Saarland, between 77% and 71% in Scotland, Slovenia, and Cracow, and were lowest in Estonia (67%). Projections for 2005–2009 predict further rises of 6%–9% units
566 | Gondos et al.
in Cracow, Slovenia, and Scotland and rises of 2%–4% units elsewhere. Among patients with corpus uteri cancer, survival rose by 10 or more % units in Geneva, Cracow, and Estonia, and between 4% and 7% units elsewhere, except for Torino and Eindhoven, where estimates remained essentially unchanged. By 2000–2004, the 5-year relative survival of patients exceeded 80% in Geneva, Saarland, Norway, Finland, and Eindhoven and ranged between 77% and 70% elsewhere. Projections for 2005–2009 predict further rises in survival in Cracow, Scotland, and Geneva and little or no change elsewhere. Among patients with ovarian cancer, increases in survival exceeded 10% units in Cracow, Saarland, Slovenia, and Finland and were between 4% and 8% units in Eindhoven, Estonia, Scotland, Norway, and Tuscany (all significant); survival remained unchanged in Geneva and Torino. By 2000–2004, the 5-year relative survival reached or exceeded 40% in Saarland, Finland, Norway, and Geneva and ranged between 38% and 30% elsewhere. Projections for 2005–2009 indicate a survival exceeding 40% in most registries under study within this time period.
trends in urological cancers Between 1990–1994 and 2000–2004, the 5-year relative survival of patients with prostate, testicular, and kidney cancers rose
Volume 20 | No. 3 | March 2009
original article
Annals of Oncology
Table 3. Trends in age-adjusted 5-year relative survival of patients with breast and female genital cancers, 1990–1994 to 2000–2004, and model-based projected survival for 2005–2009, by registry
Breast Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland Corpus Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland Ovary Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland
1990–1994 PE
SE
1995–1999 PE
51.9 58.0 63.0 76.2 79.0 73.1 64.4 78.0 74.6 76.7 73.2
1.9 1.6 1.2 1.2 1.0 1.4 0.5 0.6 0.6 1.7 1.2
58.4 60.6 69.6 75.9 71.9 79.4 65.8 76.6 74.2 70.2 78.1 21.8 21.7 26.1 31.6 32.5 28.3 27.3 31.7 34.8 37.8 29.5
Changea
P value for trend
2005–2009 PE
SE
18.7 8.2 11.0 8.5 5.9 9.8 12.2 6.6 8.5 9.9 7.2
<0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01
80.4 69.6 80.3 89.2 88.7 87.1 82.1 87.7 87.4 88.9 84.4
1.5 1.5 1.0 0.8 0.8 0.8 0.5 0.5 0.5 1.3 1.1
3.2 2.0 1.6 2.2 1.8 1.7 1.2 0.9 1.0 3.0 2.0
12.3 11.5 7.6 22.3 4.8 0.8 7.7 3.8 7.2 14.2 5.0
<0.01 <0.01 0.01 0.67 0.02 0.40 <0.01 <0.01 <0.01 0.01 0.08
76.3 73.8 79.0 72.7 79.9 81.8 78.0 82.7 84.5 88.6 84.1
3.4 2.4 2.0 3.2 2.3 2.5 1.5 1.1 1.2 3.2 2.4
2.5 1.7 1.6 2.0 1.9 1.7 0.9 1.0 1.0 3.5 2.4
13.8 8.0 11.7 1.2 4.1 8.2 7.9 10.3 7.1 1.9 12.7
<0.01 <0.01 <0.01 0.88 0.02 0.01 <0.01 <0.01 <0.01 0.35 <0.01
46.5 37.0 44.6 32.9 39.5 40.1 40.6 47.6 46.7 44.2 50.3
3.6 2.5 2.5 2.9 2.8 2.6 1.2 1.4 1.5 4.8 3.3
SE
2000–2004 PE
SE
65.5 60.6 67.9 81.2 83.3 79.8 70.8 79.6 78.7 78.3 75.7
1.9 1.4 1.1 1.0 0.9 1.0 0.5 0.5 0.6 1.5 1.1
70.6 66.2 74.0 84.7 84.9 82.9 76.6 84.6 83.1 86.6 80.4
1.6 1.4 0.9 0.9 0.8 0.7 0.5 0.5 0.5 1.3 1.0
3.2 2.2 2.1 2.4 2.0 3.0 1.4 1.1 1.2 3.7 2.2
64.7 64.5 72.9 72.3 74.9 79.3 72.4 79.2 77.9 81.2 78.7
3.4 2.2 1.8 2.2 1.9 2.1 1.3 1.0 1.1 3.6 1.9
70.7 72.1 77.2 73.6 76.7 80.2 73.5 80.4 81.4 84.4 83.1
2.3 1.7 1.7 2.5 2.1 2.4 0.8 1.0 1.0 3.3 2.1
34.6 24.9 34.8 34.0 32.4 34.0 31.1 34.3 36.5 42.6 38.1
3.0 1.6 1.8 2.1 1.9 1.9 0.8 1.0 1.0 3.8 2.3
35.6 29.7 37.8 32.8 36.6 36.5 35.2 42.0 41.9 39.7 42.2
a
Change in the 5-year relative survival between 1990–1994 and 2000–2004, in % units. PE, point estimate; SE, standard error.
significantly in 11, four, and nine of the total 11 populations under study, respectively (Table 4). Among patients with prostate cancer, survival rose greatest, by 30% units, in Torino and Cracow, and by 20%–26% units in all other registries, except Eindhoven and Saarland, where rises of 17% and 15% units, respectively, were seen. By 2000–2004, the 5-year relative survival of patients, which was <60% in 7 of 11 registries in 1990–1994, rose to at least 60% in all registries: estimates were highest in Saarland and Torino (89%), between 84% and 80% in Finland, Geneva, Eindhoven, Tuscany, and Norway and at 73% in Scotland. Survival remained <70% in Estonia, Slovenia and was lowest in Cracow (60%). Projections for 2005–2009 indicate further rises in all registries: 5-year relative survival may exceed 70% in all registries and rise above 90% in those with the highest survival in 2000–2004.
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Among patients with testicular cancer, increases in survival were more marked in Cracow (+27% units) and Estonia (+15% units), the registries with the lowest survival in 1990–1994. Elsewhere, gradual increments in survival were seen in all registries with estimates <90% in 1990–1994. Projections for 2005–2009 suggest that 5-year relative survival will reach 90% in all registries except Estonia, where survival is projected to be 82%. Among patients diagnosed with kidney cancer, marked increases in survival occurred in Estonia and Torino (+21 and +16% units, respectively), as well as in Cracow, Saarland, Tuscany, and Scotland (10%–11% units); estimates rose by 6% to 7% units in Finland, Slovenia, and Norway. The rise in Geneva (+8% units) was not statistically significant, and survival remained essentially unchanged in Eindhoven. By
doi:10.1093/annonc/mdn639 | 567
original article
Annals of Oncology
Table 4. Trends in age-adjusted 5-year relative survival of patients with common urological cancers, 1990–1994 to 2000–2004, and model-based projected survival for 2005–2009, by registry
Prostate Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland Testis Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland Kidney Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland
1990–1994 PE
SE
1995–1999 PE
31.4 44.1 42.6 57.0 55.7 64.0 50.7 60.0 58.5 62.8 73.9
4.2 2.7 2.3 3.1 2.4 2.6 1.2 1.2 1.1 3.7 2.2
59.7 59.8 88.6 88.5 84.6 96.6 88.4 88.6 94.6 97.0 89.5 33.2 38.9 45.4 55.5 60.9 50.3 33.8 49.9 49.7 53.0 58.5
Changea
P value for trend
2005–2009 PE
SE
28.2 21.8 21.5 31.7 25.6 17.4 22.0 24.2 21.1 20.5 15.4
<0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01
71.9 72.4 69.7 94.2 87.6 88.0 80.9 90.4 84.8 88.4 93.1
3.2 2.1 1.8 0.8 1.1 1.1 0.7 0.4 0.6 1.8 1.0
4.6 7.8 2.2 4.7 3.3 2.7 1.1 2.0 1.1 6.8 1.5
26.8 14.7 5.0 6.5 7.0 25.0 6.9 4.3 20.7 29.0 8.2
0.03 0.08 0.10 0.36 0.26 0.87 <0.01 0.03 0.61 0.94 0.01
89.1 81.8 95.6 95.2 93.1 91.4 97.2 95.4 94.7 95.0 98.1
4.9 6.8 1.8 3.7 3.6 3.6 0.8 1.7 1.3 5.5 1.3
3.0 2.0 1.8 2.2 1.6 1.8 1.1 1.0 1.1 4.1 2.2
11.2 20.9 6.1 16.3 10.4 20.2 9.9 6.9 5.9 8.0 10.3
0.02 <0.01 0.01 <0.01 <0.01 0.50 <0.01 <0.01 <0.01 0.13 <0.01
51.1 69.1 54.8 77.3 74.3 50.0 49.1 60.4 57.7 68.4 73.4
4.1 2.2 2.6 2.6 2.1 3.0 1.5 1.3 1.4 5.7 2.7
SE
2000–2004 PE
SE
39.8 61.6 49.9 74.3 71.8 79.8 62.4 71.1 69.5 72.3 79.4
4.2 2.2 2.0 2.3 2.0 1.5 1.0 0.9 0.8 2.5 1.7
59.6 65.9 64.1 88.7 81.3 81.4 72.7 84.2 79.6 83.3 89.3
3.1 2.0 1.5 1.4 1.4 1.1 0.8 0.5 0.6 1.6 1.3
7.2 6.9 3.5 4.0 3.9 0.0 1.8 2.7 1.2 1.7 3.6
74.3 69.2 93.4 90.9 89.7 89.4 92.9 91.1 94.0 96.0 86.1
7.4 5.8 2.6 0.0 3.6 3.2 1.4 2.0 1.2 3.3 4.4
86.5 74.5 93.6 95.0 91.6 91.6 95.3 92.9 93.9 88.0 97.7
3.2 2.4 2.4 2.8 1.9 3.5 1.2 1.1 1.2 4.6 2.6
48.4 52.7 48.4 64.6 65.6 55.4 38.4 56.0 50.7 64.5 66.1
3.2 2.1 2.2 2.4 1.7 2.3 1.2 1.0 1.1 4.4 2.4
44.4 59.8 51.5 71.8 71.3 50.1 43.7 56.8 55.6 61.0 68.8
a
Change in the 5-year relative survival between 1990–1994 and 2000–2004, in % units. PE, point estimate; SE, standard error.
2000–2004, the 5-year relative survival of patients was highest, exceeding or coming close to 70%, in Torino, Tuscany, and Saarland, while survival ranged between 61% and 50% in the other registries, except in Cracow and Scotland (both 44%). Projections for 2005–2009 indicate ongoing survival increases in all registries, except for Eindhoven.
trends in haematological cancers Between 1990–1994 and 2000–2004, the 5-year relative survival of patients diagnosed with non-Hodgkin’s lymphoma (NHL), multiple myeloma, and leukaemia rose significantly in 10, four, and five of the total 11 registries under investigation, respectively (Table 5). Among patients diagnosed with NHL, survival rises of 11%–13% units occurred in Geneva, Slovenia, Torino,
568 | Gondos et al.
Tuscany, Scotland, and Finland, while estimates rose by 6%–8% units in Cracow, Saarland, and Norway and by 3% units in Estonia. By 2000–2004, 5-year relative survival was between 62% and 51% in all registries, except in Cracow and Estonia, where survival remained <40%. Projections for the diagnostic period 2005–2009 suggest that moderate survival increases will continue in all registries except Eindhoven. Among patients with multiple myeloma, rises were marked in Tuscany, Estonia (+13% and 11% units, respectively), Scotland, and Norway (+7% and 6% units, respectively). By the 2000–2004 period, 5-year relative survival was >40% in Norway and Tuscany and ranged between 39% and 30% in all other registries, except Cracow (23%). Among patients with leukaemia, survival rises of 10% units occurred in Norway, Scotland, Slovenia, Estonia, and Tuscany,
Volume 20 | No. 3 | March 2009
original article
Annals of Oncology
Table 5. Trends in age-adjusted 5-year relative survival of patients with common haematological cancers, 1990–1994 to 2000–2004, and model-based projected survival for 2005–2009, by registry 1990–1994 PE Non-Hodgkin’s lymphoma Cracow 28.8 Estonia 35.6 Slovenia 41.7 Torino 48.2 Tuscany 45.2 Eindhoven 47.0 Scotland 41.9 Finland 42.8 Norway 49.5 Geneva 49.1 Saarland 53.1 Multiple myeloma Cracow 12.6 Estonia 18.8 Slovenia 27.5 Torino 32.1 Tuscany 36.0 Eindhoven 29.2 Scotland 26.3 Finland 31.3 Norway 36.5 Geneva 33.4 Saarland 36.5 Leukaemia Cracow 11.3 Estonia 35.1 Slovenia 31.8 Torino 34.8 Tuscany 30.0 Eindhoven 40.1 Scotland 37.5 Finland 37.3 Norway 35.8 Geneva 44.2 Saarland 42.7
SE
1995–1999 PE
5.2 3.6 2.3 2.2 1.9 4.1 1.0 1.0 1.1 3.4 2.6
Changea
P value for trend
2005–2009 PE
SE
7.6 3.2 12.4 11.8 11.4 4.1 11.3 10.9 6.3 12.8 7.5
0.04 0.03 <0.01 <0.01 <0.01 0.47 <0.01 <0.01 <0.01 <0.01 <0.01
43.4 44.5 59.5 63.1 61.0 50.8 58.2 57.9 58.1 67.2 64.5
5.0 3.5 2.4 2.3 2.2 2.7 1.2 1.1 1.3 3.8 2.9
3.5 3.5 2.6 2.9 2.5 2.4 1.4 1.3 1.4 4.8 3.2
10.4 11.4 3.7 3.6 12.7 0.4 6.9 1.3 6.4 5.6 25.0
0.43 0.01 0.52 0.14 <0.01 0.85 <0.01 0.12 0.04 0.56 0.63
22.3 34.4 30.2 39.8 55.7 28.1 36.8 29.5 42.9 40.6 32.2
5.7 4.8 3.6 4.0 3.4 3.4 1.9 1.8 1.9 7.1 4.4
3.4 2.4 1.8 2.2 2.0 1.9 1.0 1.2 1.2 3.3 2.4
10.9 8.1 8.5 9.7 8.5 4.7 10.3 2.0 12.2 10.4 1.6
0.10 <0.01 <0.01 0.09 0.02 0.07 <0.01 0.39 <0.01 0.21 0.68
24.5 47.1 44.9 45.9 39.0 45.9 53.5 39.7 52.5 54.2 44.7
4.5 3.1 2.5 3.2 2.7 3.0 1.4 1.6 1.6 4.6 3.5
SE
2000–2004 PE
SE
36.2 38.9 50.1 51.3 52.0 45.6 44.7 47.2 50.1 49.2 51.4
3.8 2.8 2.0 1.9 1.7 2.2 0.9 0.9 1.1 3.5 2.4
36.4 38.8 54.1 60.0 56.6 51.1 53.2 53.7 55.8 61.9 60.6
3.3 2.3 1.8 1.7 1.6 1.6 0.9 0.9 1.0 3.1 2.1
4.1 3.3 3.1 3.9 2.7 3.5 1.5 1.5 1.6 5.2 3.9
22.3 20.9 25.8 36.0 49.6 23.5 30.3 31.7 38.3 39.0 36.0
4.5 3.6 2.9 3.2 2.5 2.6 1.5 1.4 1.5 5.6 3.3
23.0 30.2 31.2 35.7 48.7 29.6 33.2 32.6 42.9 39.0 31.5
2.3 2.2 1.9 2.8 2.0 3.4 1.1 1.2 1.4 4.0 2.4
22.7 36.7 40.2 43.4 31.6 36.6 46.7 38.8 43.3 46.7 43.1
3.5 2.3 2.1 2.4 2.0 2.3 1.1 1.2 1.3 3.6 2.4
22.2 43.2 40.3 44.5 38.5 44.8 47.8 39.3 48.0 54.6 44.3
a
Change in the 5-year relative survival between 1990–1994 and 2000–2004, in % units. PE, point estimate; SE, standard error.
as well as in Geneva, Cracow, and Torino, but trends in the latter three registries were not significant. By 2000–2004, 5-year relative survival was highest in Geneva (at 55%), while estimates were between 48% and 38% elsewhere, except in Cracow where it remained at 22%. Projections for the 2005– 2009 period indicate ongoing survival rises in Scotland, Norway, Slovenia, and Estonia.
trends in other common cancers Between 1990–1994 and 2000–2004, the 5-year relative survival of patient diagnosed with lung and thyroid cancers rose significantly in 9 and 8 of the 11 registries, respectively, while among patients with skin melanoma, significant rises occurred in six and five of the registries among female and male patients, respectively (Table 6).
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Absolute increases in survival among patients with lung cancer were generally rather modest and <5% units, except for Geneva (+7% units). By 2000–2004, survival was highest in Geneva and Saarland (20% and 17%, respectively) and ranged between 10% and 15% elsewhere. Projections for the calendar years 2005–2009 suggest very modest rises in survival in most registries. Among patients diagnosed with cutaneous melanoma, survival was distinctly higher and rose more consistently among females than males. Differences between sexes were generally between 7% and 10% units by 2000–2004; in this diagnosis period, estimates were highest for both sexes in Geneva (97% and 87% for females and males, respectively). Elsewhere, survival among females came close to or exceeded 90% in all but four registries (Cracow, Estonia, Slovenia, and
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Table 6. Trends in age-adjusted 5-year relative survival of patients diagnosed with other common cancers, 1990–1994 to 2000–2004, and model-based projected survival for 2005–2009, by registry
Lung Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland Skin melanoma (females) Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland Skin melanoma (males) Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland Thyroid Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland
Changea
P value for trend
2005–2009 PE SE
4.3 2.1 2.4 2.6 0.2 0.7 0.6 0.1 2.7 7.0 4.7
<0.01 <0.01 <0.01 <0.01 <0.01 0.70 <0.01 0.43 <0.01 <0.01 <0.01
16.9 12.5 12.7 15.2 17.6 13.9 12.2 10.5 14.3 22.7 20.2
1.2 0.8 0.6 0.9 0.8 0.7 0.3 0.4 0.5 1.8 1.1
4.2 2.6 1.7 1.9 1.9 1.6 0.9 1.0 0.8 0.0 2.7
6.1 16.7 16.7 12.7 6.6 14.2 9.2 7.3 7.7 10.6 8.7
0.41 0.01 <0.01 <0.01 0.77 0.12 0.01 0.04 0.92 0.04 0.06
75.0 78.1 90.0 94.5 85.1 91.1 93.0 89.0 88.7 98.4 94.3
6.0 3.4 1.7 1.7 2.9 2.0 1.1 1.4 1.2 1.3 2.4
60.6 58.8 73.5 81.5 81.5 76.5 84.9 80.4 78.4 87.1 83.8
5.6 4.1 2.4 2.4 2.2 2.3 1.3 1.2 1.0 2.5 2.9
2.0 7.2 25.4 17.7 21.3 3.4 8.2 2.1 2.8 1.8 11.7
0.66 0.10 <0.01 <0.01 <0.01 0.31 <0.01 0.27 0.06 0.29 <0.01
56.2 63.6 82.0 89.0 90.7 76.5 86.6 81.0 80.8 89.0 90.1
8.3 5.6 2.5 2.6 2.0 3.2 1.5 1.8 1.4 3.4 2.8
91.5 88.9 91.4 94.6 91.8 84.6 86.0 91.1 91.7 96.3 92.1
1.7 1.8 1.3 1.2 1.1 2.3 1.3 0.7 0.9 1.5 1.9
12.5 7.7 8.7 9.0 7.4 24.8 3.4 2.9 0.1 4.9 12.0
<0.01 <0.01 <0.01 <0.01 <0.01 0.65 0.01 0.01 0.87 0.36 <0.01
94.5 92.3 93.4 97.5 95.1 84.3 87.9 92.2 91.2 94.6 94.6
1.5 1.7 1.3 0.8 1.1 3.5 1.4 0.9 1.2 2.7 1.6
1990–1994 PE SE
1995–1999 PE SE
2000–2004 PE SE
10.1 9.5 9.1 9.7 14.5 13.8 9.0 10.2 10.6 12.7 12.5
0.8 0.7 0.5 0.6 0.7 0.8 0.3 0.4 0.4 1.2 0.8
12.3 9.6 10.0 13.9 15.0 14.0 9.4 10.4 12.1 18.1 13.7
0.9 0.7 0.5 0.8 0.7 0.6 0.3 0.4 0.4 1.5 0.8
14.4 11.6 11.5 12.3 14.7 14.5 9.6 10.3 13.3 19.7 17.2
1.0 0.7 0.5 0.7 0.7 0.5 0.3 0.4 0.4 1.3 0.8
61.4 57.5 67.3 78.9 78.3 75.4 83.0 80.6 81.1 86.8 81.9
2.8 2.1 1.5 1.6 1.4 1.6 0.7 0.7 0.5 1.5 1.7
77.6 66.3 76.6 87.6 83.8 87.3 89.5 85.5 89.0 90.6 88.9
4.4 3.1 2.3 2.2 2.1 2.0 1.0 1.2 0.8 2.4 2.7
67.5 74.2 84.0 91.6 84.9 89.6 92.2 87.9 88.8 97.4 90.6
58.6 51.6 48.1 63.8 60.2 73.1 76.7 78.3 75.6 85.3 72.1
6.8 5.0 3.5 4.6 3.7 4.4 1.8 1.6 1.2 4.0 4.1
57.9 54.1 71.5 82.9 81.6 67.6 77.3 78.6 80.3 84.0 78.9
5.5 4.7 3.0 3.3 2.8 3.1 1.6 1.4 1.0 2.9 3.7
79.0 81.2 82.7 85.6 84.4 89.4 82.6 88.2 91.6 91.4 80.1
2.4 2.6 2.0 1.6 1.7 2.9 1.5 0.9 0.9 3.3 2.5
80.4 86.2 87.2 89.7 89.5 85.0 84.2 90.7 90.0 86.0 87.6
3.5 2.3 1.5 1.9 1.4 2.3 1.3 0.7 1.0 3.5 1.4
a
Change in the 5-year relative survival between 1990–1994 and 2000–2004, in % units. PE, point estimate; SE, standard error.
Tuscany), while among males, estimates were 80% in all registries except Carcow, Estonia, and Slovenia. Survival rose more markedly among males than females in Torino, Slovenia, and Tuscany, while increases were between 5% and
570 | Gondos et al.
10% units higher in females than in males in Estonia, Eindhoven, Finland, Norway, and Geneva. Projections for 2005–2009 anticipate further large increases in survival among male patients in Estonia, Slovenia, the Italian registries, and
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Saarland, with smaller survival increments in the remaining registries and among females. For patients diagnosed with thyroid cancer, fairly rapid increases in survival were observed in Cracow, Saarland, and Torino (+9%–12%), as well as in Slovenia, Estonia, and Tuscany (+7%–9% units). By 2000–2004, the 5-year relative survival exceeded or came close to 90% in all registries, except Scotland (86%) and Eindhoven (85%). Projections for 2005–2009 anticipate ongoing increases in most registries.
discussion This is the first application of model-based period analysis for comparing long-term trends in population-based cancer survival and projecting population-based cancer survival estimates within the framework of an international cooperation. Results covering the period 1990–2004 indicate ongoing survival increases in the participating registries for most common forms of cancers, including colorectal, breast, lung and prostate, as well as other important malignancies such as cutaneous melanoma, NHL, stomach, kidney, and thyroid cancers. Furthermore, patterns of geographic differences in survival identified in the 1980s and 1990s within Europe [13–16]—generally high survival in Northern Europe, lower survival in the eastern part of the continent compared with elsewhere and, with the exception of a few cancer sites, lower survival in the UK populations than in other non-Eastern parts of the continent—appear to concord with the observed and predicted survival in the first decade of the 21st century as well. The survival of colorectal cancer patients continues to be markedly lower in Cracow, Estonia, and Slovenia than elsewhere in 2000–2004, with survival estimates below those seen among the other registry populations for patients diagnosed in 1990–1994. This pattern also applied for breast and prostate cancers and for cutaneous melanoma. The survival of patients with NHL in Estonia and of patients with all haematological malignancies in Cracow was lower in 2000– 2004 when compared with survival in 1990–1994 in the other participating registries. This would suggest inadequate availability of, or access to modern, more effective forms of care for these patients. On the other hand, there has been a convergence in the survival of patients with cancers associated with good outcome if treated, such as thyroid and testicular cancers [17], and any differences may essentially disappear by 2005–2009. Incidence, survival, and mortality trends considered together may identify true progress against cancer, often marked by improving survival alongside more favourable changes in mortality than incidence [18–20]. Patterns of change in the registry-specific age-adjusted incidence and corresponding national-level mortality rates (Table 7) between 1988–1992 and 1998–2002 suggest that the survival increases more likely reflect true progress in early diagnosis and treatment for gastrointestinal cancers, melanoma, as well as breast and corpus uteri cancer, while the mortality trends confirm a lack of progress in the tertiary prevention of lung cancer. The pattern for prostate cancer, with dramatic rises in survival and incidence in most registries, is consistent with lead time and overdiagnosis effects [21, 22] caused by the increasing
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original article utilisation of prostate-specific antigen (PSA) testing as a diagnostic tool [23, 24]. Clinical studies have shown that for both stomach and colorectal cancers, advances in adjuvant therapy [25–28] and surgical management [29–31] are important in increasing survival. For breast cancer, advances in hormonal therapy [32–35], better risk assessment of patients [36], and earlier diagnosis through mass or opportunistic screening are likely to be key factors, while for ovarian cancer, improved quality of surgical management and centralisation of care are important [37, 38]. For prostate cancer, advances in therapy of both localised and metastatic diseases could play a role [39, 40], but stage shift and a lengthy lead time, mainly caused by the use of PSA testing [41] likely explain much of the apparent increases in survival. In NHL, stem-cell transplantation [42] as well as antibody therapy [43] have been shown to provide better disease control; among patients with leukaemia, improvements in the diagnosis and therapy have contributed [44, 45]. Previous analyses from collaborative international studies have suggested between-country variations in cancer survival may be largely explained by socioeconomic factors and overall health expenditures. These factors are likely to explain much of the persisting survival differences seen between Eastern and other European countries in our analysis. With increasing economic prosperity and better access to effective diagnosis and care in Eastern countries, the current survival gap could be substantially reduced. Even within the constraints of limited economic resources, improvements in survival may be achieved by actions such as concerted efforts in surgical management strategies [46] and quality control [47] in colorectal cancer, quality assurance in breast cancer-screening programmes [48], early detection programmes for melanomas of the skin [49, 50], increasing participation in clinical trials [51], and specialisation of cancer care [52]. In this paper, the combination of model-based analysis with techniques of period analysis enabled projections of survival expectations of currently diagnosed patients and thus allowed more timely monitoring of cancer survival than previous studies which primarily pertained to patients diagnosed many years ago. Clearly, the validity of the projections depends on the validity of the model assumptions, in particular the legitimacy of extrapolating trends in survival in preceding time periods. While this precondition will not always hold, extensive empirical evaluation of the method using historical data from more than half a century from one of the participating registries has shown that application of the model in the past would, on average, have provided much better predictions of survival expectations of presently diagnosed patients than other methods commonly used for population-based monitoring of cancer survival, including standard period analysis [1]. In summary, this first model-based projection of period survival estimates for recently diagnosed patients in Europe indicates that survival remains consistently lower in Eastern European populations than elsewhere for a number of frequently diagnosed forms of cancer, including breast and colorectal cancers, melanoma of the skin, and haematological malignancies. Improving outcomes in these patient populations must remain a high priority. Model-based analysis, by enabling the projection of survival trends into the
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Table 7. Changes (in %) in the age-adjusted (World Standard) incidence of common cancers in the participating registries, between 1988–1992 and 1998– 2002, and corresponding changes in national level mortalitya
Cancer site Stomach Males Change in incidence (%) Change in mortality (%) Females Change in incidence (%) Change in mortality (%) Colorectal Males Change in incidence (%) Change in mortality (%) Females Change in incidence (%) Change in mortality (%) Lung Males Change in incidence (%) Change in mortality (%) Females Change in incidence (%) Change in mortality (%) Skin melanoma Males Change in incidence (%) Change in mortality (%) Females Change in incidence (%) Change in mortality (%) Breast Change in incidence (%) Change in mortality (%) Corpus uteri Change in incidence (%) Change in mortality (%) Prostate Change in incidence (%) Change in mortality (%)
Cracow
Estonia
Slovenia
Tuscany
Torino
Eindhoven
Scotland
Finland
Norway
Geneva
Saarland
215.6 230.5
219.0 219.8
223.3 228.0
224.2 232.8
238.2 232.8
234.2 236.5
226.9 232.9
235.5 240.4
233.7 233.8
236.6 239.9
227.1 235.4
224.9 230.3
220.4 226.1
218.5 225.5
226.9 232.7
233.1 232.7
225.2 228.7
221.0 228.6
237.2 241.7
232.5 229.6
232.6 240.8
225.7 233.2
40.2 25.3
21.4 0.9
33.0 11.9
10.4 20.4
11.2 20.4
5.6 26.4
12.9 210.2
10.2 29.6
5.3 27.9
216.6 227.8
13.6 214.8
27.9 7.5
15.9 25.3
17.2 24.5
25.5 27.4
4.3 27.4
9.2 211.4
22.0 227.0
6.4 212.4
6.6 20.1
20.1 223.9
23.8 225.3
221.6 23.0
213.2 212.2
212.0 211.6
29.2 217.8
216.9 217.8
227.1 224.8
222.9 225.4
229.2 229.0
1.7 0.7
216.9 224.8
218.5 215.3
15.9 29.8
4.6 23.7
40.5 31.6
20.7 12.6
11.5 12.6
60.8 56.3
4.6 1.6
17.2 14.6
48.2 45.9
30.8 38.4
62.0 34.1
39.7 26.7
47.6 14.7b
85.3 26.5
171.0 10.9
76.3 10.9
63.5 31.4
37.8 23.5
15.6 21.2
23.0 6.6
73.2 212.1
37.1 25.0
48.5 16.2
62.6 3.9b
61.6 218.6
132.7 0.4
99.2 0.4
48.9 2.2
24.1 17.7
14.3 28.3
28.0 25.6
70.4 219.9
19.6 210.5
29.7 25.2
31.8 16.9
25.5 24.9
24.5 213.8
30.9 213.8
25.7 211.8
12.4 219.8
28.1 26.3
27.3 211.0
25.3 226.6
17.9 212.2
20.2 216.6
13.1 215.8
31.3 217.6
7.4 229.9
10.2 229.9
14.6 215.8
35.2 228.0
12.5 215.6
11.1 223.3
212.6 239.7
21.3 229.1
74.4 31.6
82.7 51.0
86.9 24.6
71.0 28.5
136.2 28.5
55.2 25.0
51.7 3.5
100.3 0.4
54.2 1.9
70.9 222.9
71.9 210.2
a
Data were obtained from the World Health Organisation Cancer Mondial Information System: (www-dep.iarc.fr). Based on the data provided by the Estonian Cancer Registry.
b
immediate present, provides a valuable tool for overcoming the delay arising from cancer registration and provides a timely means of monitoring of trends in survival and of progress against cancer.
funding European Commission (Directorate of SANCO, Luxemburg) for EUNICE.
acknowledgements Members of the EUNICE Survival Working Group: Tiiu Aareleid (National Institute for Health Development, Estonia),
572 | Gondos et al.
Freddie Bray (Cancer Registry of Norway), Hermann Brenner (German Cancer Research Center, Germany), David Brewster (Scottish Cancer Registry, Scotland, UK), Jan Willem Coebergh (Eindhoven Cancer Registry, Netherlands), Emanuele Crocetti (Florence Cancer Registry, Italy), Adam Gondos (German Cancer Research Center, Germany), Timo Hakulinen (Finnish Cancer Registry, Finland), Bernd Holleczek (Saarland Cancer Registry, Germany), Maryska Janssen-Heijnen (Eindhoven Cancer Registry, Netherlands), Juozas Kurtinaitis (Cancer Registry of Lithuania), Margit Ma¨gi (Cancer Registry of Estonia), Jadwiga Rachtan (Cracow Cancer Registry, Poland), Stefano Rosso (Piedmont (Torino) Cancer Registry, Italy), Massimo Usel (Geneva Cancer Registry, Switzerland), and Maja Primic Zˇakelj (Cancer Registry of Slovenia).
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Annals of Oncology 20: 564–573, 2009 doi:10.1093/annonc/mdn639 Published online 9 December 2008
Trends in cancer survival in 11 European populations from 1990 to 2009: a model-based analysis A. Gondos1*, F. Bray2, T. Hakulinen3, H. Brenner1 & the EUNICE Survival Working Group 1
Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Heidelberg, Germany; 2Cancer Registry of Norway, Institute of Populationbased Cancer Research, Montebello, Oslo, Norway; 3Finnish Cancer Registry, Helsinki, Finland
Received 11 July 2008; accepted 25 August 2008
Background: The timely provision and interpretation of trends in population-based cancer survival estimates is an important clinical and public health priority.
original article
Materials and methods: We examined survival trends between 1990–1994 and 2000–2004 for 15 common cancers in 10 countries from diverse areas of Europe and provide projected survival estimates for 2005–2009, using novel techniques of model-based period analysis. Results: Between 1990–1994 and 2000–2004, the 5-year relative survival increased significantly in all participating registries among patients with prostate, breast, and colorectal cancers and in at least 7 of 11 registries for stomach, corpus uteri, ovarian, kidney, and thyroid cancers, as well as for non-Hodgkin’s lymphoma. Projections suggest further substantial increases in survival in the calendar period 2005–2009. For most cancer sites amenable to effective early detection and treatment, major geographical differences persist with lower survival in Eastern European countries. Conclusions: Model-based period analysis may be useful in providing population-based cancer survival estimates for currently diagnosed cancer patients. Concerted efforts in the organisation and quality control of cancer care will be very important to achieving further improvements in cancer control in Europe, and improving outcomes in Eastern European populations remains a priority. Key words: cancer registries, neoplasms, survival
introduction
materials and methods
Commonly, a delay of 2–3 years in the availability of population-based cancer incidence data is generally unavoidable due to the time required to attain high completeness in the registration of recent cancer information. In a previous evaluation, it was shown that model-based period analysis, on incorporating long-term survival trends into the modelling of period relative survival estimates, enabled a reliable projection of survival estimates into the near future, compensating for the delay in the general provision of such estimates [1]. We applied model-based period analysis to examine trends in survival and obtain up-to-date cancer survival estimates applying the latest survival analysis techniques in combination with most up-to-date cancer registry data to provide the most timely monitoring of population-based cancer survival. The work was carried out within the framework of the EUNICE Survival Working Group, a mutual effort of 12 population-based cancer registries across Europe.
data sources
*Correspondence to: Dr A. Gondos, Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Bergheimer Str. 20, 69115 Heidelberg, Germany. Tel: +49-6221-548125; Fax: +49-6221-548142; E-mail: [email protected]
The database included relevant cancer information from 11 cancer registries with incidence and follow-up data from at least 1985 onwards. The inclusion criteria and data preparation were described in detail elsewhere [2]. Here, malignant tumours diagnosed in 1985–2004 formed the survival database, along with corresponding age, sex, and calendar period-specific life tables to enable the calculation of relative survival estimates. Table 1 provides an overview of the included registries, their underlying populations, the timeframe of the registry-specific incidence, follow-up data, and background mortality data, as utilised in this analysis.
survival analysis Five-year relative survival estimates were calculated for selected important cancers. Relative survival estimates, which quantify cancer-related excess mortality within a cancer patient population, were derived as ratios of the observed survival of the cancer patients and the expected survival of the underlying general population [3]. The latter estimate was calculated according to the Ederer II method [4]. All derived survival estimates were period estimates, which are exclusively on the basis of the survival experience of patients during the specific calendar period for which they are derived [5], and were shown to closely predict survival later observed for patients diagnosed in that period [6–8].
ª The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected]
original article
Annals of Oncology
Table 1. Participating cancer registries, underlying populations, national coverage percentage, applicable incidence and follow-up years, and life tables utilised in this analysis Registry
Country
Registry underlying population (millions)
National coverage (%)
Incidence First Last year year
Follow-up Date of last follow-up
Life tables Life tables utilised in this analysis
Cracowa Estonia Slovenia Torino Tuscany Eindhoven Scotlandb Finland Norway Geneva Saarlandc
Poland Estonia Slovenia Italy Italy The Netherlands UK Finland Norway Switzerland Germany
0.8 1.4 1.9 1.0 1.2 1.0 5.1 5.2 4.5 0.4 1.0
1.9 100 100 1.8 2.1 6.6 100 100 100 5.3 1.3
1985 1985 1985 1985 1985 1985 1985 1985 1985 1985 1985
31/12/2004 31/12/2004 31/12/2004 31/12/2004 31/12/2004 31/12/2004 31/12/2004 31/12/2004 31/12/2004 31/12/2004 31/12/2004
1990–1991, 1990–1994, 1990–1994, 1990–1994, 1990–1994, 1990–1994, 1986–1991, 1986–1990, 1990–1994, 1990–1994, 1990–1994,
2004 2003 2003 2004 2003 2004 2004 2004 2004 2004 2004
1995–1999, 1995–1999, 1995–1999, 1995–1999, 1995–1999, 1995–1999, 1992–1997, 1991–1995, 1995–1999, 1995–1999, 1995–1999,
2000–2004 2000–2004 2000–2004 2000–2004 2000–2003 2000–2004 1998–2003 1996–2000, 2001–2004 2000–2004 2000–2004 2000–2004
a
Life table data for Poland from the HLD (www.lifetable.de) were used; for calendar years with no corresponding life table data, the life tables of the preceding or following periods were used. b All data for Scotland were on the basis of the data available from the HLD. c Life tables were derived from mortality data by the authors. HLD, Human Life-Table Database.
survival trends between 1990–1994 and 2005–2009 First, 5-year relative survival estimates were calculated for the calendar periods 1990–1994, 1995–1999, and 2000–2004: after age group-specific person-time at risk and number of deaths by year of follow-up were calculated for each period separately (i.e. 1990–1994, 1995–1999, and 2000–2004), a period-specific Poisson regression model for relative survival was used to model the excess number of deaths as a function age group (categorical variable) and follow-up year (categorical variable), using the logarithm of the person-time at risk as the offset. To derive a test of survival trends as well as projected survival estimates, the age group-specific persontime at risk and numbers of deaths by year of follow-up for the periods 1990–1994, 1995–1999, and 2000–2004 were combined and used in a common Poisson regression model, in which calendar period was included as an additional numerical term (1990–1994 = 1, 1995–1999 = 2, 2000–2004 = 3). Projected age group-specific excess number of deaths for each year of follow-up in the period 2005–2009 were obtained assuming that the trend from the periods 1990–1994 to 2000–2004 would continue into the next period. Five-year cumulative relative survival estimates were calculated by multiplication of conditional survival estimates predicted from the regression models for each year of follow-up. In both the period-specific and trend analyses, in instances where registries had data available on incident cases until 2003, but follow-up of vital status until 2004, hybrid analysis was used. The method enables estimation of up-to-date survival for situations where mortality data are available for more recent periods than incidence [9, 10]. Standard errors of the survival estimates were calculated using the delta method. Alpha = 0.05 was used as level of significance for trend tests.
age adjustment All survival estimates were age-adjusted, on the basis of five age groups (15–44, 45–54, 55–64, 65–74, 75+ years), with the exception of prostate cancer, for which the first age group was 15–54 years, and thyroid cancer, for which only two age groups were used (15–44, 45+). Adjustment was done by deriving weighted averages of modelled age-specific 5-year relative survival estimates, with weights from the International Cancer Survival
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Standards [11]. All calculations were carried out using the SAS statistical software package [12].
sponsors The funding source had no involvement in the carrying out this study.
results long-term trends in 5-year relative survival Tables 2–6 present in a uniform layout, age-adjusted 5-year relative survival estimates for 1990–1994, 1995–1999, 2000– 2004, along with model-based projected survival estimates for the calendar period 2005–2009 for the major gastrointestinal, gynaecological, urological, haematological, and other common cancers, respectively. Standard errors for the survival estimates and P values for the survival trend between 1990–1994 and 2000–2004 are also provided. trends in major gastrointestinal cancers Between 1990–1994 and 2000–2004, the 5-year relative survival of patients diagnosed with stomach and colorectal cancers rose significantly in nine and 11 of 11 registries, respectively (Table 2). Among patients with stomach cancer, major increases (of between 5% and 9% units) occurred in Saarland, Slovenia, Torino, Estonia, and Tuscany. In 2000–2004, survival was highest in Saarland (37%), while estimates ranged between 33% and 24% elsewhere, but were lower in Eindhoven (21%), Cracow, and Scotland (both 18%). Projections for the calendar years 2005–2009 predict 5-year relative survival between 19% and 40% in the participating registry populations. Increases in the survival of patients with colorectal cancer were highest, exceeding 10% units, in Cracow, Torino, Estonia, Saarland, Slovenia, and Scotland. Elsewhere, increases were
doi:10.1093/annonc/mdn639 | 565
original article
Annals of Oncology
Table 2. Trends in age-adjusted 5-year relative survival of patients diagnosed with stomach and colorectal cancers, 1990–1994 to 2000–2004, and modelbased projected survival for 2005–2009, by registry
Stomach Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland Colorectal Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland
1990–1994 PE
SE
1995–1999 PE
15.9 19.2 18.1 25.4 28.1 23.6 14.1 24.6 23.6 26.7 27.7
1.7 0.9 0.9 1.5 1.0 1.8 0.6 0.7 0.8 3.1 1.5
22.5 36.1 35.9 45.7 51.1 53.2 42.9 50.2 51.9 54.6 50.7
1.6 1.1 0.9 1.1 0.9 1.3 0.5 0.6 0.5 1.9 1.0
Changea
SE
2000–2004 PE
SE
19.1 20.8 19.6 28.5 30.8 21.5 15.1 26.4 21.7 38.1 29.5
1.7 1.0 0.9 1.6 1.1 1.3 0.6 0.8 0.9 3.7 1.6
17.9 24.1 24.3 30.6 32.8 21.0 17.7 27.7 25.3 25.9 36.8
2.0 1.1 1.0 1.7 1.2 1.2 0.7 0.8 1.0 3.3 1.8
34.9 42.6 38.9 55.2 56.3 53.7 48.2 55.5 55.6 58.7 54.3
1.7 1.1 0.8 1.1 0.8 0.9 0.5 0.6 0.5 1.7 1.0
38.7 49.1 46.9 58.3 59.7 56.2 53.5 57.9 59.2 63.5 61.9
1.6 1.1 0.8 1.0 0.8 0.8 0.5 0.6 0.5 1.7 0.9
P value for trend
2005–2009 PE
SE
2.0 4.9 6.2 5.2 4.7 22.6 3.6 3.1 1.7 20.8 9.1
0.01 <0.01 <0.01 <0.01 <0.01 0.08 <0.01 <0.01 0.02 0.35 <0.01
23.2 26.5 26.1 34.3 34.1 19.1 20.9 29.7 26.0 33.7 39.7
2.5 1.4 1.3 2.1 1.4 1.7 0.9 1.1 1.2 4.9 2.3
16.2 13.0 11.0 12.6 8.6 3.0 10.6 7.7 7.3 8.9 11.2
<0.01 <0.01 <0.01 <0.01 <0.01 0.03 <0.01 <0.01 <0.01 <0.01 <0.01
52.4 57.1 51.7 64.8 64.1 57.2 58.6 62.3 61.9 67.1 66.6
2.1 1.4 1.1 1.2 1.0 1.2 0.6 0.8 0.6 2.2 1.2
a
Change in the 5-year relative survival between 1990–1994 and 2000–2004, in % units PE, point estimate; SE, standard error.
close to 10% units in Geneva, Tuscany, Finland, and Norway, while estimates rose by 3% units in Eindhoven. In the 2000–2004 period, survival exceeded or essentially reached 60% in Geneva, Saarland, Norway, Tuscany, Torino, and Finland, ranged between 56% and 53% in Eindhoven and Scotland, but remained <50% in Estonia (49%), Slovenia (47%), and Cracow (39%). Projections for 2005–2009 predict ongoing survival increases in all registries except Eindhoven, with estimates reaching 65% in Geneva, Saarland, and Torino, and exceeding 60% in Finland and Norway.
breast and female genital cancers Between 1990–1994 and 2000–2004, the 5-year relative survival of patients diagnosed with breast, corpus, and ovarian cancers rose significantly in 11, 8, and 9 registries, respectively (Table 3). Among patients with breast cancer, increases in survival were largest in Cracow with +19% units, while increases were between 10% and 12% units in Scotland, Slovenia, Geneva, and Eindhoven, and between 8% and 6% units in the remaining registries. By 2000–2004, survival estimates ranged between 87% and 80% in Geneva, Tuscany, Torino, Finland, Norway, Eindhoven, and Saarland, between 77% and 71% in Scotland, Slovenia, and Cracow, and were lowest in Estonia (67%). Projections for 2005–2009 predict further rises of 6%–9% units
566 | Gondos et al.
in Cracow, Slovenia, and Scotland and rises of 2%–4% units elsewhere. Among patients with corpus uteri cancer, survival rose by 10 or more % units in Geneva, Cracow, and Estonia, and between 4% and 7% units elsewhere, except for Torino and Eindhoven, where estimates remained essentially unchanged. By 2000–2004, the 5-year relative survival of patients exceeded 80% in Geneva, Saarland, Norway, Finland, and Eindhoven and ranged between 77% and 70% elsewhere. Projections for 2005–2009 predict further rises in survival in Cracow, Scotland, and Geneva and little or no change elsewhere. Among patients with ovarian cancer, increases in survival exceeded 10% units in Cracow, Saarland, Slovenia, and Finland and were between 4% and 8% units in Eindhoven, Estonia, Scotland, Norway, and Tuscany (all significant); survival remained unchanged in Geneva and Torino. By 2000–2004, the 5-year relative survival reached or exceeded 40% in Saarland, Finland, Norway, and Geneva and ranged between 38% and 30% elsewhere. Projections for 2005–2009 indicate a survival exceeding 40% in most registries under study within this time period.
trends in urological cancers Between 1990–1994 and 2000–2004, the 5-year relative survival of patients with prostate, testicular, and kidney cancers rose
Volume 20 | No. 3 | March 2009
original article
Annals of Oncology
Table 3. Trends in age-adjusted 5-year relative survival of patients with breast and female genital cancers, 1990–1994 to 2000–2004, and model-based projected survival for 2005–2009, by registry
Breast Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland Corpus Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland Ovary Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland
1990–1994 PE
SE
1995–1999 PE
51.9 58.0 63.0 76.2 79.0 73.1 64.4 78.0 74.6 76.7 73.2
1.9 1.6 1.2 1.2 1.0 1.4 0.5 0.6 0.6 1.7 1.2
58.4 60.6 69.6 75.9 71.9 79.4 65.8 76.6 74.2 70.2 78.1 21.8 21.7 26.1 31.6 32.5 28.3 27.3 31.7 34.8 37.8 29.5
Changea
P value for trend
2005–2009 PE
SE
18.7 8.2 11.0 8.5 5.9 9.8 12.2 6.6 8.5 9.9 7.2
<0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01
80.4 69.6 80.3 89.2 88.7 87.1 82.1 87.7 87.4 88.9 84.4
1.5 1.5 1.0 0.8 0.8 0.8 0.5 0.5 0.5 1.3 1.1
3.2 2.0 1.6 2.2 1.8 1.7 1.2 0.9 1.0 3.0 2.0
12.3 11.5 7.6 22.3 4.8 0.8 7.7 3.8 7.2 14.2 5.0
<0.01 <0.01 0.01 0.67 0.02 0.40 <0.01 <0.01 <0.01 0.01 0.08
76.3 73.8 79.0 72.7 79.9 81.8 78.0 82.7 84.5 88.6 84.1
3.4 2.4 2.0 3.2 2.3 2.5 1.5 1.1 1.2 3.2 2.4
2.5 1.7 1.6 2.0 1.9 1.7 0.9 1.0 1.0 3.5 2.4
13.8 8.0 11.7 1.2 4.1 8.2 7.9 10.3 7.1 1.9 12.7
<0.01 <0.01 <0.01 0.88 0.02 0.01 <0.01 <0.01 <0.01 0.35 <0.01
46.5 37.0 44.6 32.9 39.5 40.1 40.6 47.6 46.7 44.2 50.3
3.6 2.5 2.5 2.9 2.8 2.6 1.2 1.4 1.5 4.8 3.3
SE
2000–2004 PE
SE
65.5 60.6 67.9 81.2 83.3 79.8 70.8 79.6 78.7 78.3 75.7
1.9 1.4 1.1 1.0 0.9 1.0 0.5 0.5 0.6 1.5 1.1
70.6 66.2 74.0 84.7 84.9 82.9 76.6 84.6 83.1 86.6 80.4
1.6 1.4 0.9 0.9 0.8 0.7 0.5 0.5 0.5 1.3 1.0
3.2 2.2 2.1 2.4 2.0 3.0 1.4 1.1 1.2 3.7 2.2
64.7 64.5 72.9 72.3 74.9 79.3 72.4 79.2 77.9 81.2 78.7
3.4 2.2 1.8 2.2 1.9 2.1 1.3 1.0 1.1 3.6 1.9
70.7 72.1 77.2 73.6 76.7 80.2 73.5 80.4 81.4 84.4 83.1
2.3 1.7 1.7 2.5 2.1 2.4 0.8 1.0 1.0 3.3 2.1
34.6 24.9 34.8 34.0 32.4 34.0 31.1 34.3 36.5 42.6 38.1
3.0 1.6 1.8 2.1 1.9 1.9 0.8 1.0 1.0 3.8 2.3
35.6 29.7 37.8 32.8 36.6 36.5 35.2 42.0 41.9 39.7 42.2
a
Change in the 5-year relative survival between 1990–1994 and 2000–2004, in % units. PE, point estimate; SE, standard error.
significantly in 11, four, and nine of the total 11 populations under study, respectively (Table 4). Among patients with prostate cancer, survival rose greatest, by 30% units, in Torino and Cracow, and by 20%–26% units in all other registries, except Eindhoven and Saarland, where rises of 17% and 15% units, respectively, were seen. By 2000–2004, the 5-year relative survival of patients, which was <60% in 7 of 11 registries in 1990–1994, rose to at least 60% in all registries: estimates were highest in Saarland and Torino (89%), between 84% and 80% in Finland, Geneva, Eindhoven, Tuscany, and Norway and at 73% in Scotland. Survival remained <70% in Estonia, Slovenia and was lowest in Cracow (60%). Projections for 2005–2009 indicate further rises in all registries: 5-year relative survival may exceed 70% in all registries and rise above 90% in those with the highest survival in 2000–2004.
Volume 20 | No. 3 | March 2009
Among patients with testicular cancer, increases in survival were more marked in Cracow (+27% units) and Estonia (+15% units), the registries with the lowest survival in 1990–1994. Elsewhere, gradual increments in survival were seen in all registries with estimates <90% in 1990–1994. Projections for 2005–2009 suggest that 5-year relative survival will reach 90% in all registries except Estonia, where survival is projected to be 82%. Among patients diagnosed with kidney cancer, marked increases in survival occurred in Estonia and Torino (+21 and +16% units, respectively), as well as in Cracow, Saarland, Tuscany, and Scotland (10%–11% units); estimates rose by 6% to 7% units in Finland, Slovenia, and Norway. The rise in Geneva (+8% units) was not statistically significant, and survival remained essentially unchanged in Eindhoven. By
doi:10.1093/annonc/mdn639 | 567
original article
Annals of Oncology
Table 4. Trends in age-adjusted 5-year relative survival of patients with common urological cancers, 1990–1994 to 2000–2004, and model-based projected survival for 2005–2009, by registry
Prostate Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland Testis Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland Kidney Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland
1990–1994 PE
SE
1995–1999 PE
31.4 44.1 42.6 57.0 55.7 64.0 50.7 60.0 58.5 62.8 73.9
4.2 2.7 2.3 3.1 2.4 2.6 1.2 1.2 1.1 3.7 2.2
59.7 59.8 88.6 88.5 84.6 96.6 88.4 88.6 94.6 97.0 89.5 33.2 38.9 45.4 55.5 60.9 50.3 33.8 49.9 49.7 53.0 58.5
Changea
P value for trend
2005–2009 PE
SE
28.2 21.8 21.5 31.7 25.6 17.4 22.0 24.2 21.1 20.5 15.4
<0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01
71.9 72.4 69.7 94.2 87.6 88.0 80.9 90.4 84.8 88.4 93.1
3.2 2.1 1.8 0.8 1.1 1.1 0.7 0.4 0.6 1.8 1.0
4.6 7.8 2.2 4.7 3.3 2.7 1.1 2.0 1.1 6.8 1.5
26.8 14.7 5.0 6.5 7.0 25.0 6.9 4.3 20.7 29.0 8.2
0.03 0.08 0.10 0.36 0.26 0.87 <0.01 0.03 0.61 0.94 0.01
89.1 81.8 95.6 95.2 93.1 91.4 97.2 95.4 94.7 95.0 98.1
4.9 6.8 1.8 3.7 3.6 3.6 0.8 1.7 1.3 5.5 1.3
3.0 2.0 1.8 2.2 1.6 1.8 1.1 1.0 1.1 4.1 2.2
11.2 20.9 6.1 16.3 10.4 20.2 9.9 6.9 5.9 8.0 10.3
0.02 <0.01 0.01 <0.01 <0.01 0.50 <0.01 <0.01 <0.01 0.13 <0.01
51.1 69.1 54.8 77.3 74.3 50.0 49.1 60.4 57.7 68.4 73.4
4.1 2.2 2.6 2.6 2.1 3.0 1.5 1.3 1.4 5.7 2.7
SE
2000–2004 PE
SE
39.8 61.6 49.9 74.3 71.8 79.8 62.4 71.1 69.5 72.3 79.4
4.2 2.2 2.0 2.3 2.0 1.5 1.0 0.9 0.8 2.5 1.7
59.6 65.9 64.1 88.7 81.3 81.4 72.7 84.2 79.6 83.3 89.3
3.1 2.0 1.5 1.4 1.4 1.1 0.8 0.5 0.6 1.6 1.3
7.2 6.9 3.5 4.0 3.9 0.0 1.8 2.7 1.2 1.7 3.6
74.3 69.2 93.4 90.9 89.7 89.4 92.9 91.1 94.0 96.0 86.1
7.4 5.8 2.6 0.0 3.6 3.2 1.4 2.0 1.2 3.3 4.4
86.5 74.5 93.6 95.0 91.6 91.6 95.3 92.9 93.9 88.0 97.7
3.2 2.4 2.4 2.8 1.9 3.5 1.2 1.1 1.2 4.6 2.6
48.4 52.7 48.4 64.6 65.6 55.4 38.4 56.0 50.7 64.5 66.1
3.2 2.1 2.2 2.4 1.7 2.3 1.2 1.0 1.1 4.4 2.4
44.4 59.8 51.5 71.8 71.3 50.1 43.7 56.8 55.6 61.0 68.8
a
Change in the 5-year relative survival between 1990–1994 and 2000–2004, in % units. PE, point estimate; SE, standard error.
2000–2004, the 5-year relative survival of patients was highest, exceeding or coming close to 70%, in Torino, Tuscany, and Saarland, while survival ranged between 61% and 50% in the other registries, except in Cracow and Scotland (both 44%). Projections for 2005–2009 indicate ongoing survival increases in all registries, except for Eindhoven.
trends in haematological cancers Between 1990–1994 and 2000–2004, the 5-year relative survival of patients diagnosed with non-Hodgkin’s lymphoma (NHL), multiple myeloma, and leukaemia rose significantly in 10, four, and five of the total 11 registries under investigation, respectively (Table 5). Among patients diagnosed with NHL, survival rises of 11%–13% units occurred in Geneva, Slovenia, Torino,
568 | Gondos et al.
Tuscany, Scotland, and Finland, while estimates rose by 6%–8% units in Cracow, Saarland, and Norway and by 3% units in Estonia. By 2000–2004, 5-year relative survival was between 62% and 51% in all registries, except in Cracow and Estonia, where survival remained <40%. Projections for the diagnostic period 2005–2009 suggest that moderate survival increases will continue in all registries except Eindhoven. Among patients with multiple myeloma, rises were marked in Tuscany, Estonia (+13% and 11% units, respectively), Scotland, and Norway (+7% and 6% units, respectively). By the 2000–2004 period, 5-year relative survival was >40% in Norway and Tuscany and ranged between 39% and 30% in all other registries, except Cracow (23%). Among patients with leukaemia, survival rises of 10% units occurred in Norway, Scotland, Slovenia, Estonia, and Tuscany,
Volume 20 | No. 3 | March 2009
original article
Annals of Oncology
Table 5. Trends in age-adjusted 5-year relative survival of patients with common haematological cancers, 1990–1994 to 2000–2004, and model-based projected survival for 2005–2009, by registry 1990–1994 PE Non-Hodgkin’s lymphoma Cracow 28.8 Estonia 35.6 Slovenia 41.7 Torino 48.2 Tuscany 45.2 Eindhoven 47.0 Scotland 41.9 Finland 42.8 Norway 49.5 Geneva 49.1 Saarland 53.1 Multiple myeloma Cracow 12.6 Estonia 18.8 Slovenia 27.5 Torino 32.1 Tuscany 36.0 Eindhoven 29.2 Scotland 26.3 Finland 31.3 Norway 36.5 Geneva 33.4 Saarland 36.5 Leukaemia Cracow 11.3 Estonia 35.1 Slovenia 31.8 Torino 34.8 Tuscany 30.0 Eindhoven 40.1 Scotland 37.5 Finland 37.3 Norway 35.8 Geneva 44.2 Saarland 42.7
SE
1995–1999 PE
5.2 3.6 2.3 2.2 1.9 4.1 1.0 1.0 1.1 3.4 2.6
Changea
P value for trend
2005–2009 PE
SE
7.6 3.2 12.4 11.8 11.4 4.1 11.3 10.9 6.3 12.8 7.5
0.04 0.03 <0.01 <0.01 <0.01 0.47 <0.01 <0.01 <0.01 <0.01 <0.01
43.4 44.5 59.5 63.1 61.0 50.8 58.2 57.9 58.1 67.2 64.5
5.0 3.5 2.4 2.3 2.2 2.7 1.2 1.1 1.3 3.8 2.9
3.5 3.5 2.6 2.9 2.5 2.4 1.4 1.3 1.4 4.8 3.2
10.4 11.4 3.7 3.6 12.7 0.4 6.9 1.3 6.4 5.6 25.0
0.43 0.01 0.52 0.14 <0.01 0.85 <0.01 0.12 0.04 0.56 0.63
22.3 34.4 30.2 39.8 55.7 28.1 36.8 29.5 42.9 40.6 32.2
5.7 4.8 3.6 4.0 3.4 3.4 1.9 1.8 1.9 7.1 4.4
3.4 2.4 1.8 2.2 2.0 1.9 1.0 1.2 1.2 3.3 2.4
10.9 8.1 8.5 9.7 8.5 4.7 10.3 2.0 12.2 10.4 1.6
0.10 <0.01 <0.01 0.09 0.02 0.07 <0.01 0.39 <0.01 0.21 0.68
24.5 47.1 44.9 45.9 39.0 45.9 53.5 39.7 52.5 54.2 44.7
4.5 3.1 2.5 3.2 2.7 3.0 1.4 1.6 1.6 4.6 3.5
SE
2000–2004 PE
SE
36.2 38.9 50.1 51.3 52.0 45.6 44.7 47.2 50.1 49.2 51.4
3.8 2.8 2.0 1.9 1.7 2.2 0.9 0.9 1.1 3.5 2.4
36.4 38.8 54.1 60.0 56.6 51.1 53.2 53.7 55.8 61.9 60.6
3.3 2.3 1.8 1.7 1.6 1.6 0.9 0.9 1.0 3.1 2.1
4.1 3.3 3.1 3.9 2.7 3.5 1.5 1.5 1.6 5.2 3.9
22.3 20.9 25.8 36.0 49.6 23.5 30.3 31.7 38.3 39.0 36.0
4.5 3.6 2.9 3.2 2.5 2.6 1.5 1.4 1.5 5.6 3.3
23.0 30.2 31.2 35.7 48.7 29.6 33.2 32.6 42.9 39.0 31.5
2.3 2.2 1.9 2.8 2.0 3.4 1.1 1.2 1.4 4.0 2.4
22.7 36.7 40.2 43.4 31.6 36.6 46.7 38.8 43.3 46.7 43.1
3.5 2.3 2.1 2.4 2.0 2.3 1.1 1.2 1.3 3.6 2.4
22.2 43.2 40.3 44.5 38.5 44.8 47.8 39.3 48.0 54.6 44.3
a
Change in the 5-year relative survival between 1990–1994 and 2000–2004, in % units. PE, point estimate; SE, standard error.
as well as in Geneva, Cracow, and Torino, but trends in the latter three registries were not significant. By 2000–2004, 5-year relative survival was highest in Geneva (at 55%), while estimates were between 48% and 38% elsewhere, except in Cracow where it remained at 22%. Projections for the 2005– 2009 period indicate ongoing survival rises in Scotland, Norway, Slovenia, and Estonia.
trends in other common cancers Between 1990–1994 and 2000–2004, the 5-year relative survival of patient diagnosed with lung and thyroid cancers rose significantly in 9 and 8 of the 11 registries, respectively, while among patients with skin melanoma, significant rises occurred in six and five of the registries among female and male patients, respectively (Table 6).
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Absolute increases in survival among patients with lung cancer were generally rather modest and <5% units, except for Geneva (+7% units). By 2000–2004, survival was highest in Geneva and Saarland (20% and 17%, respectively) and ranged between 10% and 15% elsewhere. Projections for the calendar years 2005–2009 suggest very modest rises in survival in most registries. Among patients diagnosed with cutaneous melanoma, survival was distinctly higher and rose more consistently among females than males. Differences between sexes were generally between 7% and 10% units by 2000–2004; in this diagnosis period, estimates were highest for both sexes in Geneva (97% and 87% for females and males, respectively). Elsewhere, survival among females came close to or exceeded 90% in all but four registries (Cracow, Estonia, Slovenia, and
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Table 6. Trends in age-adjusted 5-year relative survival of patients diagnosed with other common cancers, 1990–1994 to 2000–2004, and model-based projected survival for 2005–2009, by registry
Lung Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland Skin melanoma (females) Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland Skin melanoma (males) Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland Thyroid Cracow Estonia Slovenia Torino Tuscany Eindhoven Scotland Finland Norway Geneva Saarland
Changea
P value for trend
2005–2009 PE SE
4.3 2.1 2.4 2.6 0.2 0.7 0.6 0.1 2.7 7.0 4.7
<0.01 <0.01 <0.01 <0.01 <0.01 0.70 <0.01 0.43 <0.01 <0.01 <0.01
16.9 12.5 12.7 15.2 17.6 13.9 12.2 10.5 14.3 22.7 20.2
1.2 0.8 0.6 0.9 0.8 0.7 0.3 0.4 0.5 1.8 1.1
4.2 2.6 1.7 1.9 1.9 1.6 0.9 1.0 0.8 0.0 2.7
6.1 16.7 16.7 12.7 6.6 14.2 9.2 7.3 7.7 10.6 8.7
0.41 0.01 <0.01 <0.01 0.77 0.12 0.01 0.04 0.92 0.04 0.06
75.0 78.1 90.0 94.5 85.1 91.1 93.0 89.0 88.7 98.4 94.3
6.0 3.4 1.7 1.7 2.9 2.0 1.1 1.4 1.2 1.3 2.4
60.6 58.8 73.5 81.5 81.5 76.5 84.9 80.4 78.4 87.1 83.8
5.6 4.1 2.4 2.4 2.2 2.3 1.3 1.2 1.0 2.5 2.9
2.0 7.2 25.4 17.7 21.3 3.4 8.2 2.1 2.8 1.8 11.7
0.66 0.10 <0.01 <0.01 <0.01 0.31 <0.01 0.27 0.06 0.29 <0.01
56.2 63.6 82.0 89.0 90.7 76.5 86.6 81.0 80.8 89.0 90.1
8.3 5.6 2.5 2.6 2.0 3.2 1.5 1.8 1.4 3.4 2.8
91.5 88.9 91.4 94.6 91.8 84.6 86.0 91.1 91.7 96.3 92.1
1.7 1.8 1.3 1.2 1.1 2.3 1.3 0.7 0.9 1.5 1.9
12.5 7.7 8.7 9.0 7.4 24.8 3.4 2.9 0.1 4.9 12.0
<0.01 <0.01 <0.01 <0.01 <0.01 0.65 0.01 0.01 0.87 0.36 <0.01
94.5 92.3 93.4 97.5 95.1 84.3 87.9 92.2 91.2 94.6 94.6
1.5 1.7 1.3 0.8 1.1 3.5 1.4 0.9 1.2 2.7 1.6
1990–1994 PE SE
1995–1999 PE SE
2000–2004 PE SE
10.1 9.5 9.1 9.7 14.5 13.8 9.0 10.2 10.6 12.7 12.5
0.8 0.7 0.5 0.6 0.7 0.8 0.3 0.4 0.4 1.2 0.8
12.3 9.6 10.0 13.9 15.0 14.0 9.4 10.4 12.1 18.1 13.7
0.9 0.7 0.5 0.8 0.7 0.6 0.3 0.4 0.4 1.5 0.8
14.4 11.6 11.5 12.3 14.7 14.5 9.6 10.3 13.3 19.7 17.2
1.0 0.7 0.5 0.7 0.7 0.5 0.3 0.4 0.4 1.3 0.8
61.4 57.5 67.3 78.9 78.3 75.4 83.0 80.6 81.1 86.8 81.9
2.8 2.1 1.5 1.6 1.4 1.6 0.7 0.7 0.5 1.5 1.7
77.6 66.3 76.6 87.6 83.8 87.3 89.5 85.5 89.0 90.6 88.9
4.4 3.1 2.3 2.2 2.1 2.0 1.0 1.2 0.8 2.4 2.7
67.5 74.2 84.0 91.6 84.9 89.6 92.2 87.9 88.8 97.4 90.6
58.6 51.6 48.1 63.8 60.2 73.1 76.7 78.3 75.6 85.3 72.1
6.8 5.0 3.5 4.6 3.7 4.4 1.8 1.6 1.2 4.0 4.1
57.9 54.1 71.5 82.9 81.6 67.6 77.3 78.6 80.3 84.0 78.9
5.5 4.7 3.0 3.3 2.8 3.1 1.6 1.4 1.0 2.9 3.7
79.0 81.2 82.7 85.6 84.4 89.4 82.6 88.2 91.6 91.4 80.1
2.4 2.6 2.0 1.6 1.7 2.9 1.5 0.9 0.9 3.3 2.5
80.4 86.2 87.2 89.7 89.5 85.0 84.2 90.7 90.0 86.0 87.6
3.5 2.3 1.5 1.9 1.4 2.3 1.3 0.7 1.0 3.5 1.4
a
Change in the 5-year relative survival between 1990–1994 and 2000–2004, in % units. PE, point estimate; SE, standard error.
Tuscany), while among males, estimates were 80% in all registries except Carcow, Estonia, and Slovenia. Survival rose more markedly among males than females in Torino, Slovenia, and Tuscany, while increases were between 5% and
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10% units higher in females than in males in Estonia, Eindhoven, Finland, Norway, and Geneva. Projections for 2005–2009 anticipate further large increases in survival among male patients in Estonia, Slovenia, the Italian registries, and
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Saarland, with smaller survival increments in the remaining registries and among females. For patients diagnosed with thyroid cancer, fairly rapid increases in survival were observed in Cracow, Saarland, and Torino (+9%–12%), as well as in Slovenia, Estonia, and Tuscany (+7%–9% units). By 2000–2004, the 5-year relative survival exceeded or came close to 90% in all registries, except Scotland (86%) and Eindhoven (85%). Projections for 2005–2009 anticipate ongoing increases in most registries.
discussion This is the first application of model-based period analysis for comparing long-term trends in population-based cancer survival and projecting population-based cancer survival estimates within the framework of an international cooperation. Results covering the period 1990–2004 indicate ongoing survival increases in the participating registries for most common forms of cancers, including colorectal, breast, lung and prostate, as well as other important malignancies such as cutaneous melanoma, NHL, stomach, kidney, and thyroid cancers. Furthermore, patterns of geographic differences in survival identified in the 1980s and 1990s within Europe [13–16]—generally high survival in Northern Europe, lower survival in the eastern part of the continent compared with elsewhere and, with the exception of a few cancer sites, lower survival in the UK populations than in other non-Eastern parts of the continent—appear to concord with the observed and predicted survival in the first decade of the 21st century as well. The survival of colorectal cancer patients continues to be markedly lower in Cracow, Estonia, and Slovenia than elsewhere in 2000–2004, with survival estimates below those seen among the other registry populations for patients diagnosed in 1990–1994. This pattern also applied for breast and prostate cancers and for cutaneous melanoma. The survival of patients with NHL in Estonia and of patients with all haematological malignancies in Cracow was lower in 2000– 2004 when compared with survival in 1990–1994 in the other participating registries. This would suggest inadequate availability of, or access to modern, more effective forms of care for these patients. On the other hand, there has been a convergence in the survival of patients with cancers associated with good outcome if treated, such as thyroid and testicular cancers [17], and any differences may essentially disappear by 2005–2009. Incidence, survival, and mortality trends considered together may identify true progress against cancer, often marked by improving survival alongside more favourable changes in mortality than incidence [18–20]. Patterns of change in the registry-specific age-adjusted incidence and corresponding national-level mortality rates (Table 7) between 1988–1992 and 1998–2002 suggest that the survival increases more likely reflect true progress in early diagnosis and treatment for gastrointestinal cancers, melanoma, as well as breast and corpus uteri cancer, while the mortality trends confirm a lack of progress in the tertiary prevention of lung cancer. The pattern for prostate cancer, with dramatic rises in survival and incidence in most registries, is consistent with lead time and overdiagnosis effects [21, 22] caused by the increasing
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original article utilisation of prostate-specific antigen (PSA) testing as a diagnostic tool [23, 24]. Clinical studies have shown that for both stomach and colorectal cancers, advances in adjuvant therapy [25–28] and surgical management [29–31] are important in increasing survival. For breast cancer, advances in hormonal therapy [32–35], better risk assessment of patients [36], and earlier diagnosis through mass or opportunistic screening are likely to be key factors, while for ovarian cancer, improved quality of surgical management and centralisation of care are important [37, 38]. For prostate cancer, advances in therapy of both localised and metastatic diseases could play a role [39, 40], but stage shift and a lengthy lead time, mainly caused by the use of PSA testing [41] likely explain much of the apparent increases in survival. In NHL, stem-cell transplantation [42] as well as antibody therapy [43] have been shown to provide better disease control; among patients with leukaemia, improvements in the diagnosis and therapy have contributed [44, 45]. Previous analyses from collaborative international studies have suggested between-country variations in cancer survival may be largely explained by socioeconomic factors and overall health expenditures. These factors are likely to explain much of the persisting survival differences seen between Eastern and other European countries in our analysis. With increasing economic prosperity and better access to effective diagnosis and care in Eastern countries, the current survival gap could be substantially reduced. Even within the constraints of limited economic resources, improvements in survival may be achieved by actions such as concerted efforts in surgical management strategies [46] and quality control [47] in colorectal cancer, quality assurance in breast cancer-screening programmes [48], early detection programmes for melanomas of the skin [49, 50], increasing participation in clinical trials [51], and specialisation of cancer care [52]. In this paper, the combination of model-based analysis with techniques of period analysis enabled projections of survival expectations of currently diagnosed patients and thus allowed more timely monitoring of cancer survival than previous studies which primarily pertained to patients diagnosed many years ago. Clearly, the validity of the projections depends on the validity of the model assumptions, in particular the legitimacy of extrapolating trends in survival in preceding time periods. While this precondition will not always hold, extensive empirical evaluation of the method using historical data from more than half a century from one of the participating registries has shown that application of the model in the past would, on average, have provided much better predictions of survival expectations of presently diagnosed patients than other methods commonly used for population-based monitoring of cancer survival, including standard period analysis [1]. In summary, this first model-based projection of period survival estimates for recently diagnosed patients in Europe indicates that survival remains consistently lower in Eastern European populations than elsewhere for a number of frequently diagnosed forms of cancer, including breast and colorectal cancers, melanoma of the skin, and haematological malignancies. Improving outcomes in these patient populations must remain a high priority. Model-based analysis, by enabling the projection of survival trends into the
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Table 7. Changes (in %) in the age-adjusted (World Standard) incidence of common cancers in the participating registries, between 1988–1992 and 1998– 2002, and corresponding changes in national level mortalitya
Cancer site Stomach Males Change in incidence (%) Change in mortality (%) Females Change in incidence (%) Change in mortality (%) Colorectal Males Change in incidence (%) Change in mortality (%) Females Change in incidence (%) Change in mortality (%) Lung Males Change in incidence (%) Change in mortality (%) Females Change in incidence (%) Change in mortality (%) Skin melanoma Males Change in incidence (%) Change in mortality (%) Females Change in incidence (%) Change in mortality (%) Breast Change in incidence (%) Change in mortality (%) Corpus uteri Change in incidence (%) Change in mortality (%) Prostate Change in incidence (%) Change in mortality (%)
Cracow
Estonia
Slovenia
Tuscany
Torino
Eindhoven
Scotland
Finland
Norway
Geneva
Saarland
215.6 230.5
219.0 219.8
223.3 228.0
224.2 232.8
238.2 232.8
234.2 236.5
226.9 232.9
235.5 240.4
233.7 233.8
236.6 239.9
227.1 235.4
224.9 230.3
220.4 226.1
218.5 225.5
226.9 232.7
233.1 232.7
225.2 228.7
221.0 228.6
237.2 241.7
232.5 229.6
232.6 240.8
225.7 233.2
40.2 25.3
21.4 0.9
33.0 11.9
10.4 20.4
11.2 20.4
5.6 26.4
12.9 210.2
10.2 29.6
5.3 27.9
216.6 227.8
13.6 214.8
27.9 7.5
15.9 25.3
17.2 24.5
25.5 27.4
4.3 27.4
9.2 211.4
22.0 227.0
6.4 212.4
6.6 20.1
20.1 223.9
23.8 225.3
221.6 23.0
213.2 212.2
212.0 211.6
29.2 217.8
216.9 217.8
227.1 224.8
222.9 225.4
229.2 229.0
1.7 0.7
216.9 224.8
218.5 215.3
15.9 29.8
4.6 23.7
40.5 31.6
20.7 12.6
11.5 12.6
60.8 56.3
4.6 1.6
17.2 14.6
48.2 45.9
30.8 38.4
62.0 34.1
39.7 26.7
47.6 14.7b
85.3 26.5
171.0 10.9
76.3 10.9
63.5 31.4
37.8 23.5
15.6 21.2
23.0 6.6
73.2 212.1
37.1 25.0
48.5 16.2
62.6 3.9b
61.6 218.6
132.7 0.4
99.2 0.4
48.9 2.2
24.1 17.7
14.3 28.3
28.0 25.6
70.4 219.9
19.6 210.5
29.7 25.2
31.8 16.9
25.5 24.9
24.5 213.8
30.9 213.8
25.7 211.8
12.4 219.8
28.1 26.3
27.3 211.0
25.3 226.6
17.9 212.2
20.2 216.6
13.1 215.8
31.3 217.6
7.4 229.9
10.2 229.9
14.6 215.8
35.2 228.0
12.5 215.6
11.1 223.3
212.6 239.7
21.3 229.1
74.4 31.6
82.7 51.0
86.9 24.6
71.0 28.5
136.2 28.5
55.2 25.0
51.7 3.5
100.3 0.4
54.2 1.9
70.9 222.9
71.9 210.2
a
Data were obtained from the World Health Organisation Cancer Mondial Information System: (www-dep.iarc.fr). Based on the data provided by the Estonian Cancer Registry.
b
immediate present, provides a valuable tool for overcoming the delay arising from cancer registration and provides a timely means of monitoring of trends in survival and of progress against cancer.
funding European Commission (Directorate of SANCO, Luxemburg) for EUNICE.
acknowledgements Members of the EUNICE Survival Working Group: Tiiu Aareleid (National Institute for Health Development, Estonia),
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Freddie Bray (Cancer Registry of Norway), Hermann Brenner (German Cancer Research Center, Germany), David Brewster (Scottish Cancer Registry, Scotland, UK), Jan Willem Coebergh (Eindhoven Cancer Registry, Netherlands), Emanuele Crocetti (Florence Cancer Registry, Italy), Adam Gondos (German Cancer Research Center, Germany), Timo Hakulinen (Finnish Cancer Registry, Finland), Bernd Holleczek (Saarland Cancer Registry, Germany), Maryska Janssen-Heijnen (Eindhoven Cancer Registry, Netherlands), Juozas Kurtinaitis (Cancer Registry of Lithuania), Margit Ma¨gi (Cancer Registry of Estonia), Jadwiga Rachtan (Cracow Cancer Registry, Poland), Stefano Rosso (Piedmont (Torino) Cancer Registry, Italy), Massimo Usel (Geneva Cancer Registry, Switzerland), and Maja Primic Zˇakelj (Cancer Registry of Slovenia).
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